Research in this project is currently focused on four areas. These are characterization of the survivors of the anthrax attacks of 2001; evaluation of the factors underlying pathogenicity in cytokine expressing ectromelia; characterization of emerging respiratory infections including SARS and influenza; and development of novel therapies for avian flu. The anthrax study has enrolled a cohort of volunteers who are currently undergoing an extensive diagnostic evaluation. A study in non-human primates determined that post-exposure vaccination plus antibiotics was superior to antibiotics alone as a means of preventing the development of inhalational anthrax following exposure to anthrax spores. To be ready to deal with emerging infectious diseases of the respiratory tract, a protocol has been developed to systematically study patients presenting with a compatible symptom complex. This protocol has been complemented by the development of treatment protocol that will utilize hyperimmune Ig to the SARS virus. In response to the threat of avian influenza, in collaboration with the World Health Organization, the Welcome Trust and a series of academic and government organizations, a clinical research network has been established in SE Asia that will be able to conduct studies focused on the characterization and treatment of emerging influenza outbreaks. The first protocol in this network will examine the effects of standard vs. double dose oseltamivir in treating severe cases of influenza. To explore novel therapeutic approaches to avian influenza a protocol is in development to hyperimmunize normal volunteers with an H5N1 vaccine. If a strong immune response can be generated in this way; the plasma from these volunteers will be utilized to generate a hyperimmune Ig.